Variant 17-81650758-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002602.4(PDE6G):c.*316G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 483,768 control chromosomes in the GnomAD database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 252 hom., cov: 32)

Exomes 𝑓: 0.045 ( 697 hom. )

Consequence

PDE6G
NM_002602.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.926

Variant links:

Genes affected

PDE6G (HGNC:8789): (phosphodiesterase 6G) This gene encodes the gamma subunit of cyclic GMP-phosphodiesterase, which is composed of alpha- and beta- catalytic subunits and two identical, inhibitory gamma subunits. This gene is expressed in rod photoreceptors and functions in the phototransduction signaling cascade. It is also expressed in a variety of other tissues, and has been shown to regulate the c-Src protein kinase and G-protein-coupled receptor kinase 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

PDE6G links:

PDE6G (HGNC:):

PDE6G links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 17-81650758-C-T is Benign according to our data. Variant chr17-81650758-C-T is described in ClinVar as [Benign]. Clinvar id is 325856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE6G	NM_002602.4 linkuse as main transcript	c.*316G>A		3_prime_UTR_variant	4/4	ENST00000331056.10	NP_002593.1	P18545

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDE6G	ENST00000331056.10 linkuse as main transcript	c.*316G>A	3_prime_UTR_variant	4/4	1	NM_002602.4	ENSP00000328412.5	P18545
PDE6G	ENST00000574024.1 linkuse as main transcript	n.513G>A	non_coding_transcript_exon_variant	3/3	1
PDE6G	ENST00000574777.1 linkuse as main transcript	n.480G>A	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0425

AC:

6463

AN:

151940

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0372

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.0640

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0341

Gnomad OTH

AF:

0.0316

GnomAD3 exomes

AF:

0.0500

AC:

6082

AN:

121520

Hom.:

344

AF XY:

0.0496

AC XY:

3276

AN XY:

66030

show subpopulations

Gnomad AFR exome

AF:

0.0427

Gnomad AMR exome

AF:

0.0236

Gnomad ASJ exome

AF:

0.0191

Gnomad EAS exome

AF:

0.211

Gnomad SAS exome

AF:

0.0560

Gnomad FIN exome

AF:

0.0128

Gnomad NFE exome

AF:

0.0348

Gnomad OTH exome

AF:

0.0386

GnomAD4 exome

AF:

0.0450

AC:

14913

AN:

331710

Hom.:

697

Cov.:

AF XY:

0.0453

AC XY:

8349

AN XY:

184480

show subpopulations

Gnomad4 AFR exome

AF:

0.0417

Gnomad4 AMR exome

AF:

0.0235

Gnomad4 ASJ exome

AF:

0.0186

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.0560

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0343

Gnomad4 OTH exome

AF:

0.0456

GnomAD4 genome

AF:

0.0426

AC:

6473

AN:

152058

Hom.:

252

Cov.:

AF XY:

0.0420

AC XY:

3119

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0438

Gnomad4 AMR

AF:

0.0372

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.0641

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.0341

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0180

Hom.:

Bravo

AF:

0.0451

Asia WGS

AF:

0.131

AC:

456

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over